Andrew Bellinger’s career spans the full arc of translational medicine — from seeing patients as a cardiologist, to co-founding Lyndra Therapeutics out of his postdoctoral research, to helping bring Verve’s base editing technology to the clinic as CSO, and now introducing a new immunotherapy paradigm as co-founder of Corner Therapeutics.
Andrew joined me to share what it takes to build new drug modalities from scratch, the bold bets and tough calls that shaped Verve’s journey, and lessons in building new companies from first-in-class science. — Sajith Wickramasekara
* Editor’s note: The conversation has been edited for length and clarity.
Verve’s bold vision — and contrarian bet on product, not platform
Sajith Wickramasekara: Founded in 2018, Verve Therapeutics advanced three in vivo gene editing products (including two to the clinic), and was recently acquired by Eli Lilly.
At launch, Verve was distinctively focused on a single therapeutic area, when every new biotech was building a platform. That was a very contrarian decision at the time. Can you talk more about the founding of Verve and the decision to focus on a single therapeutic area?
Andrew Bellinger: Verve was founded on the principle that we were going to develop in vivo gene editing medicines for cardiovascular disease. This was also a very contrarian bet because, at the time, gene therapy was primarily for rare diseases.
“The concept that you could apply gene editing to a common disease was sort of hard to believe. People thought we were crazy for a couple reasons.”
One, people didn't believe that gene editing — a brand new technology that had just been invented — would be something patients and even doctors might be comfortable using for a common disease.
Two, common diseases already have some therapies. They may not work all that well sometimes, but we have therapy options.
Sajith: Like statins for cardiovascular disease.
Andrew: Exactly. The idea that you would use gene editing for a common disease that has alternative therapies was controversial. But in practice, we need more treatment options for patients.
So this concept forced us to make a couple decisions. These development programs were going to be bigger, which meant we probably couldn't do ten of them.
Sajith: Just because of cost?
Andrew: Yeah, we were going to have to be more focused. The company was founded with four cardiovascular targets. We only had a license to the base editing technology from Beam Therapeutics for those four targets.
So in some ways, it was a function of necessity. We didn't have the option of being a platform that could go after a hundred rare diseases. We made that bet right at the founding to be a product-focused company.
Sajith: Was there ever pressure to go broader, as the company reached certain milestones?
Andrew: Yeah, and we did. The pressure came from the public and investors. One of the criticisms of Verve publicly was that we didn't have a platform and that limited the upside in some sense.
Our counterargument was that we were treating the most common disease in the world.
“As one of our founders liked to say, if all we do is cure coronary disease, we've done enough.”
We did end up broadening focus over time and adding programs outside of those four targets, including a program with Vertex that was for a serious liver condition. But only after we had established the company. This gets at a broader point about that tension between product and platform.
Sajith: How should biotech entrepreneurs think about platform versus products? It feels like a pendulum that just swings back and forth. Again, when Verve was founded, platform was distinctly in fashion — and today, it's like a bad word.
Andrew: The fundamental challenge with a platform approach is that without the clarifying focus of a product, you have this tendency to build capabilities that you hope will eventually lead to a product. But that creates all kinds of misaligned incentives.
Usually, if you're developing even one product, you have to build an awful lot of platform behind it. We did, at Verve. We built a ton of platform capabilities, but it was all geared towards product development.
That’s the mental model that I advocated for at Verve, which was to focus the entire company on one thing at first. As you do that, you're going to build a lot of capabilities that allow you to scale and potentially go in other directions. Then you can make careful decisions about when and how to do that.
“If you start the company and really focus it at the beginning on one product, you'll build the muscles that will eventually allow you to do more.“
Sajith: I find this really interesting because in the tech world, every great platform has come out of a killer application. You back the platform out over time, and the application earns you permission to keep going on the platform.
Do you think entrepreneurs are just too scared of seeming narrow by going after a single product? Do they think investors want them to say, “We're going to take over the world with this amazing platform that will cure all diseases?”
Andrew: Absolutely. Also, in the gene therapy and gene editing world — where a lot of companies are going after rare diseases — the commercial opportunity of their first product sometimes doesn't actually justify the effort. So they have to believe that if I do this easy problem first, then I can do this harder problem later.
We were fortunate at Verve, to have a clinical development plan that let us do that. Meaning, we could go after a rare disease first, specifically people with a genetic underlying risk or condition that increases their cardiovascular risk.
Why Verve has been called “the best-run biotech”
Sajith: A lot of people have told me that Verve was one of the best-run biotech companies that they've ever worked at. Verve also went from founding to clinical trials in just four years, which by biotech standards is fast — it’s unbelievably fast when you consider that this was a brand new modality.
What made Verve so special, either from an operational or strategic standpoint? What helped Verve move so fast?
Andrew: I think focus was critical in moving fast, and in building a culture that was very results-oriented.
“Nothing undermines an organization and culture more than people having uncertainty about what the priorities are, or why they're working on something. That has a pervasive effect.”
The other is hiring. Sek Kathiresan [CEO of Verve] and I both interviewed every single applicant for the first 150 positions. That’s about a thousand applicants over the first few years.
Verve ended up being around 285 people. We continued to interview almost everybody.
Sajith: Why did you do that?
Andrew: We told ourselves that there’s no higher value function that executives can do than hiring well. But I think it's more than just hiring well. It's also the message that you send to the organization by doing that.
Sajith: I bet every single person coming in felt a higher purpose knowing that the founder, the CEO, and the head of R&D had all personally interviewed them.
Andrew: People would say, ”I've never interviewed with a CEO or a CSO before in my career, and I've been at ten companies.”
It says to the applicants: you're important, we care, we want to know you. We think it's important that we hire talent well. It says to the organization that you prioritize quality.
Sajith: Did the organization look at you and Sek as a bottleneck sometimes?
Andrew: Totally, but in a way that highlighted that we cared about cultural factors and emotional intelligence. That was what we were interviewing for. We weren't interviewing for technical skills. It highlighted to the organization that they couldn't just sneak somebody through because they really needed help with some problem that they needed to solve.
Sajith: Did it affect the types of roles that Verve hired for?
Andrew: I believe very strongly that the performance of an organization has a lot to do with not just the people you bring in, but how you put them together.
One of the mistakes that early biotechs make is trying to build an org chart based on what they think biotech should look like. This idea that there should be C-suite executives, vice presidents, and functions reporting in a certain way.
Often, it's trying to make a twenty-person biotech look like a pharma company. Which is insane when you say it like that. But the temptation is real. Actually, there's a lot of pressure to do that.
Sajith: Where does the pressure come from?
Andrew: Investors want to see a mature organization. What we did at Verve was a little different. Again, we were focused on one product at first, so we built basically a project team, which meant a very flat organization.
We hired people who were really strong in their domains and put them together so that they could focus on moving the project forward, rather than on building fiefdoms.
“There was no incentive to build capabilities — we were all just trying to make a product.“
That played a big role in our ability to move fast, and also to maintain a mission-driven culture of people who were focused on advancing this really challenging new modality for a huge problem in the world.
Paying the pioneer’s tax
Sajith: Verve was the first to bring base editing to the clinic. In the past, you’ve mentioned the concept of a “pioneer's tax.” What is that? And what were some of the biggest challenges you faced with navigating regulatory authorities for a brand new modality?
Andrew: The first challenge was just that everyone thought we were crazy.
“In Silicon Valley, maybe everyone's a pioneer. But in biotech, being a pioneer is not necessarily a good thing.”
Investors and regulators like things that are precedented. When you're doing something that's never been done before, everyone has lots of questions.
Biotech’s really hard, and it's so easy to fail. When you make it even harder by doing something in a new way, you're just upping the ante for investors and regulators.
When we submitted the first IND for an in vivo gene editing medicine to the FDA, they suddenly had to think about all the implications.
Sajith: The regulator has never done this before, so they don't even know what they're looking for, I assume.
Andrew: They don't have a playbook. So that can raise scientific or policy questions. In our case, in vivo gene editing raised a profound policy question: could editing the patient in front of you also mean editing future generations of humanity?
Sajith: That’s a little scary when you phrase it like that.
Andrew: The FDA understandably had a lot of questions. It was uncertain even what the bar for that risk should be: 0.001%? Does it have to be 0%? And how do you prove 0% risk? What experiment could you run to prove that?
When you submit the first IND, you have to tackle all those issues in real time. So today, just three or four years later, when a company submits an IND for in vivo gene editing medicine, the FDA has thought about these issues now. There’s a playbook of how to handle this, and companies are routinely now navigating it without too much struggle. But when you're the first, you pay that tax.
Gene editing’s “iPhone moment”
Sajith: A few years ago, people were comparing gene editing to the Motorola “bag phone” era — promising but very early. What does the iPhone moment for gene editing looks like? Did we just see it with Verve co-founder Kiran Musunuru and the treatment of baby KJ Muldoon?
Andrew: First of all, I'm incredibly proud of Kiran and for what he’s accomplished with baby KJ. It definitely captured the public’s mind in a way that other moments haven't.
I would say this is a moment where people are reassessing whether the pessimism of the last few years was overdone. But I don't know that it’s the iPhone moment.
I think the iPhone moment will come with the first commercial success of a gene editing therapy. That's sort of the analogy to the iPhone — that it was launched and suddenly the demand was enormous.
That's what gene editing needs — the realization that patients and doctors will embrace this, in contrast to everyone’s caution now.
If you asked me to predict, I think Alpha-1 Antitrypsin programs have the potential for being that moment. It's a disease with essentially no treatment options, it can be very severe, and impacts a lot of people. And the therapies look like they're gonna work.
So I can see that being a moment where the generalist investors that have moved away from gene editing in a profound way over the last few years see that this technology can impact a lot of patients and actually be commercially viable.
Leaving medicine to become an entrepreneur
Sajith: Let's talk about the company you co-founded and ran for a while before Verve. During your cardiology fellowship, you did a postdoc in Bob Langer's lab, which led to co-founding Lyndra Therapeutics.
Did you always plan on becoming an entrepreneur? What was the transition from medicine to industry like?
Andrew: I think everyone who spends time in Bob Langer's lab is motivated because they want to have an impact. That's a unifying feature of Bob's lab, and I like the self-fulfilling nature of it. It attracts more people who want to have an impact.
In hindsight, the decision to work with Bob was an indication that I was certainly open to it. I will say it surprised my wife quite a bit. She did not expect me to stop being a doctor and become an entrepreneur.
Sajith: So you were seeing patients at the time?
Andrew: I continued to see patients for a long time after, probably another seven or eight years. I only gave it up a few years ago, largely because it was becoming increasingly challenging to navigate that while also leading a public company.
Sajith: What’s Lyndra’s founding story?
Andrew: We had a really interesting solution to a problem: adherence to oral therapies is really poor. We had developed this long-acting oral technology in the Langer Lab. But was this a commercially viable strategy? And could we make work in humans? It wasn’t obvious.
We spent a long time mulling over whether this could be a developable drug. And eventually, we decided it was. I'm very grateful to Amy Schulman for that decision. She was the first CEO, and I was the CSO. I was essentially a cardiologist with very limited experience in industry at the time, so she took a big chance on me.
We built the company and got several programs into the clinic. I think we accomplished a lot in moving the technology forward.
But thinking about how hard it is to be a patient is a really profound thing that we don't always do a great job of thinking about.
Sajith: It's very easy to get absorbed in the technology and science and forget that at the end of day, a patient's got to take the drug.
Andrew: That's right. And what's their experience of their disease, and the condition of taking the medicine even?
A patient once told me why he wasn't taking his medicine after a heart attack. I asked why he wasn't taking it to prevent another one. He said that every time he did, he was reminded of the heart attack and felt sick. That’s stuck with me ever since.
It’s a profound example of how differently patients think about medicine compared to doctors or drug developers. Patients are very focused on living their lives as well as they can — which they should be.
Sajith: You led Lyndra from its early concept in the lab to phase I clinical trials. What told you it was time for your next chapter, and that Verve was it?
Andrew: This may sound a little insecure, but when you've founded a company and grown it, you might question: Did I get really lucky? Could I do this again, or was that my one shot at success?
I'm somebody who's very motivated by having a chip on my shoulder — in a constructive way, I hope. The idea of doing it again was really appealing, proving to myself that I could.
Why Verve? A one-time gene editing therapy that can lower your risk of cardiovascular disease for the rest of your life, potentially — that's a profound concept. It’s not even about the data; it's a change in the way we think about medicine.
We've thought about gene therapies in the context of cures for horrible diseases. That's the mental model that most people have for gene editing and gene therapy. But you can envision a different model where one-time therapies become almost a molecular surgery to prevent future diseases. That's a radical concept.
Are we there now? No. Are we going to be there in 5-10 years? Probably not. But the idea of Verve was so profound that I had to work on it.
I distinctly remember saying to myself: This has the potential to be the most important advance in cardiovascular disease care in the next 50 years. Once you make that statement in your head, you have to take that shot.
Sajith: Lyndra wound down this year due to the tough funding environment. What was your reaction and how did it make you feel?
Andrew: Biotech is a really hard business. A lot of things have to go right for a company to be successful. It's not just about whether the technology or drug works.
Maintaining consistent funding momentum through ups and downs is super challenging. Maintaining continuity of people and governance by the board and investors is also really challenging. So it makes me a little sad, especially given the incredible effort of so many people at Lyndra over 10+ years.
Mainly, I wish that the technology and the progress that was made could’ve found a home. That would’ve been a more satisfying outcome, even if it hadn't been a great financial return for anyone. It's unfortunate that it wound down the way it did. But sometimes things don't work out the way you hope.
Why you can’t turn science off and on
Sajith: As a clinician-scientist and now an entrepreneur, you've seen everything from academic research to drug discovery to patient care. What's your reaction to the current administration’s cuts to scientific agencies and the pressure on universities today?
Andrew: I think multiple things can be true at the same time. There has been a lot of need for reform in the way academic science is done. There's a lot of administrative bloat; there's a lot of regulatory capture and rent-seeking across the ecosystem. There was a lot of need for change.
Unfortunately, the change that we're getting is (I’ll call it, optimistically) a creative destruction model: the idea that if we break everything, then a thousand flowers will bloom and a new model will magically appear.
“I worry that with science, you can't turn it off and on very quickly. It's a very slow accretion of knowledge, training, and experience.”
This kind of disruption has the potential to have profound negative repercussions. The transitory shocks right now are distressing and, certainly on an individual level, can be very harmful for a lot of the scientists who are impacted.
But the more structural impacts worry me in the longer term. Like a risk-off mentality that leads to a pretty profound shrinking of the ambition of science in America.
Also it's unfortunate that it's happening when the biotech industry is not in a position to really absorb the impact. Had we been in a different moment in the cycle, there would have been more potential for private industry to step in and buffer some of the impacts.
“We happen to be at a moment where industry is pulling back and becoming less ambitious at the same time that academic and government-funded scientific enterprises are hurting.”
Why tough feedback (and tough problems) are a gift
Sajith: Success in biotech to me is both about taking big risks and also learning from great mentors. You mentioned Amy Schulman. Can you talk about her and others who’ve had an impact on you?
Andrew: I could list a half dozen people and say with confidence, that I would not be here today without them. Mentors play such an important role in most entrepreneurs' experience.
A lot of people think of mentors as people who can open doors for you, and that's certainly true. Amy is a great example — she took a chance on me. I don't even know what she saw that made her do that, but she did. And I'm incredibly grateful for that.
But it's actually not what I'm most grateful for. I'm most grateful for all the negative feedback she gave me.
Sajith: Any examples you care to share?
Andrew: Amy profoundly changed my leadership style — and who I am. She taught me emotional intelligence, how to think like an investor or pharma executive, and how to communicate.
One of my first pitches to a pharma company was with Amy. She had worked in Pfizer in a very senior role, while I was basically a scientist fresh out of the Langer Lab.
We did a 40-minute pitch where I talked about the technology, the science, and how we could collaborate with them. After, Amy sat me down, and for 90 minutes — twice as long as the meeting itself — she gave me detailed notes about everything I did wrong. Like very detailed feedback about how I answered questions.
People always ask, what's the biggest mistake scientists make in talking? Amy drilled this into me over and over again: scientists don't answer the question first. Answer the question, and then you can say whatever you want afterwards.
Amy broke me down a bit. It took away a lot of my confidence, which I gradually built back up again.
“I’m profoundly grateful for all that negative feedback. I’ve learned, with more maturity and time, how much of an investment it was.”
It was an amazing amount of emotional energy, mental energy, and time that she invested in me, by telling me what I was doing wrong.
Sajith: You've touched so many different technologies and therapeutic areas — Cocoon Biotech on developing silkworm protein for drug delivery, Lyndra on long-acting oral drugs, Verve on gene therapies for cardiovascular disease, and Corner Therapeutic for durable immunity against cancer.
What’s the through line? What keeps you going?
Andrew: It's less about the science of individual targets or biology pathways, and much more about how we alter the patient experience of illness.
In the case of Corner Therapeutics, it's cancer vaccines — a concept that was very exciting 10-20 years ago, but fell out of favor. I think we'll see a resurgence in the next few years.
The idea of a therapy that either prevents progression of a cancer or treats the cancer as a vaccine — it's just a powerful concept. It’s these kinds of ideas that motivate me. All of these are hard problems.
Hard problems have this tendency to attract the best people to them — because they come together with a mission to solve a hard problem. An easy problem is not going to attract the best people to it. Hard problems are what bring the best people together.
